No abstract

The evolution of selfing taxa from outcrossing ancestors has occurred repeatedly and is the subject of many theoretical models, yet few empirical studies have examined the immediate consequences of inbreeding in a population with variable expression of self‐incompatibility. Because self‐incompatibility breaks down with floral age in Campanula rapunculoides, we were able to mate outbred and selfed maternal plants in a crossing design which produced progeny with inbreeding coefficients of 0, 0.25, 0.50 and 0.75. Cumulative inbreeding depression in plants that were selfed for one generation was very high in families derived from strongly self‐incompatible plants (average δ = 0.98), and somewhat lower in families derived from plants with weaker expression of self‐incompatibility (average δ = 0.90). Relative to outbred progeny, inbred progeny produced fewer seeds, had lower rates of germination, less vegetative growth and fewer flowers per plant. Inbred progeny also took longer to germinate, and longer to produce a first leaf and to flower. Interestingly, inbred plants also produced 40% fewer seeds than outcrossed plants (t‐test P < 0.001) even when mated to the same, unrelated pollen donor, suggesting that inbreeding can produce profound maternal effects. Most importantly, our results demonstrate that progeny derived from plants with stronger expression of self‐incompatibility exhibited greater levels of inbreeding depression than progeny from plants with weaker expression of self‐incompatibility. Moreover, the decline in fitness (cumulative, ln‐transformed) over the four inbreeding levels was steeper for the progeny of the strongly self‐incompatible lineages. These empirical results suggest that inbreeding depression and mating system phenotype have the potential to coevolve.

BACKGROUND AND PURPOSERenal ischaemia-reperfusion (IR) injury is an inevitable consequence of renal transplantation, causing significant graft injury, increasing the risk of rejection and contributing to poor long-term graft outcome. Renal injury is mediated by cytokine and chemokine synthesis, inflammation and oxidative stress resulting from activation of the NF-kB pathway. EXPERIMENTAL APPROACHWe utilized liposomal incorporation of a potent inhibitor of the NF-kB pathway, curcumin, to target delivery to renal tubular epithelial and antigen-presenting cells. Liposomes containing curcumin were administered before bilateral renal ischaemia in C57/B6 mice, with subsequent reperfusion. Renal function was assessed from plasma levels of urea and creatinine, 4 and 24 h after reperfusion. Renal tissue was examined for NF-kB activity and oxidative stress (histology, immunostaining) and for apoptosis (TUNEL). Cytokines and chemokines were measured by RT-PCR and Western blotting. KEY RESULTSLiposomal curcumin significantly improved serum creatinine, reduced histological injury and cellular apoptosis and lowered Toll-like receptor-4, heat shock protein-70 and TNF-a mRNA expression. Liposomal curcumin also reduced neutrophil infiltration and diminished inflammatory chemokine expression. Curcumin liposomes reduced intracellular superoxide generation and increased superoxide dismutase levels, decreased inducible NOS mRNA expression and 3-nitrotyrosine staining consistent with limitations in nitrosative stress and inhibited renal tubular mRNA and protein expression of thioredoxin-interacting protein. These actions of curcumin were mediated by inhibition of NF-kB, MAPK and phospho-S6 ribosomal protein. CONCLUSIONS AND IMPLICATIONSLiposomal delivery of curcumin promoted effective, targeted delivery of this non-toxic compound that provided cytoprotection via anti-inflammatory and multiple antioxidant mechanisms following renal IR injury.

Background People with intellectual disabilities (IDs) have very high rates of osteoporosis and fractures, to which their widespread vitamin D deficiency and other factors could contribute. We aimed to assess in people with IDs previously treated for vitamin D deficiency (1) long-term adherence to vitamin D supplementation and (2) bone mineral density (BMD), as an indicator for risk of fractures, according to vitamin D supplementation and other factors. Method We recorded height, weight, medical, pharmacological, dietary and lifestyle assessment. Blood sample were taken for vitamin D and related analytes. dual-energy X-ray absorptiometry for BMD was performed. Results Of 51 study participants (mean [standard deviation, SD] age 51.5 [13.6] years, 57% male), 41 (80.4%) were taking vitamin D and 10 were not. Mean [SD] serum vitamin D was 81.3 [21.3] vs. 25.2 [10.2] nmol/L (P < 0.0001), respectively. Thirty-six participants underwent a dual-energy X-ray absorptiometry scan, which showed osteoporosis in 23.7%

Although there is a safe, inexpensive and efficacious vaccine against yellow fever, vaccination against other flavivirus diseases is less successful. There is no licensed vaccine against dengue fever and current vaccines against tick-borne encephalitis (TBE) and Japanese encephalitis are expensive and require several injections. Furthermore novel vaccines containing only virus envelope proteins may raise fears over antibody mediated enhancement (ADE) of disease. Here we report the successful use of genetic vaccination against TBE in an experimental animal model using a plasmid containing the coding sequence of a non-structural protein (NS1). Such vaccines would provide inexpensive protection against disease, without raising concerns over inducing ADE on subsequent exposure to heterotypic infectious virus. Attempts to generate chaemeric plasmids to protect against both TBE and dengue fever were less successful. Although these chaemeric plasmids directed the synthesis and secretion of the virus NS1 protein normally, no protection was observed against either TBE or dengue fever.